The general aim of this project is to obtain a more precise understanding of multiple immunological and genetic factors possibly related singly or in combination to the pathogenesis of multiple sclerosis. These include: (1) Determination of histocompatibility types in a carefully selected population of MS patients and appropriate controls. (2) Correlation of histocompatibility data with the humoral and cell-mediated immune response to viruses. (3) Identification of new lymphocyte antigens which may show greater correlation with multiple sclerosis than presently identified lymphocyte antigens. (4) Evaluation of cerebrospinal fluid immunoglobulin content and specificity. (5) Evaluation of families with a multiple incidence of multiple sclerosis and examination of affected and nonaffected members of these families with respect to the above. To minimize some of the variables in the disease, identical and nonidentical twins who are either discordant or concordant for MS are being studied. (6) Similar studies are being conducted in patients with SSPE.